Some medical conditions are best treated by administration of a pharmaceutical or other active substance which is formulated to allow the active substance or ingredient to act as quickly as possible. Such a formulation may comprise an injectable solution, suspension, or a readily dissolvable tablet or capsule. This type of formulation is useful, for instance, for treating acute pain, such as headaches, or pain associated with sudden trauma, such as an accident.
Other medical conditions are best treated by administration of a pharmaceutical or other active substance in such a way as to sustain its action over an extended period of time. This type of administration is useful, for example, for treating chronic pain, such as that associated with rheumatic or arthritic conditions, for the treatment of a chronic cardiovascular condition, or for administering an antibiotic in a course of treatment covering several days. Sustained action can be achieved by repeated administration of an immediate-release tablet or capsule at frequent intervals, for instance every four hours. However, this is generally inconvenient, especially during the night, when it is often necessary to awaken a patient to administer the suspension, tablet or capsule. In addition, such multiple dosing may lead to undesirable fluctuations in the plasma concentration of the active substance.
It has previously been proposed to produce a formulation which will release the active substance therein at a controlled rate such that the amount available in the body to treat the condition is maintained at a therapeutic level over an extended period of time. Particularly suitable periods are twelve hours and twenty-four hours, since such formulations need only be taken once or twice a day to maintain an effective treatment of the condition. Such formulations are generally known as "sustained-release formulations."
Many sustained-release formulations are already known, but there is no generally applicable method by which such formulations can be designed. Generally speaking, each sustained-released formulation is dependent on the particular active substance incorporated therein. In designing a formulation, it is generally necessary to take into account many factors, including the rates of absorption and clearance of the active substance, the interaction of the active substance with the excipients and/or coating to be used in the formulation, the solubility of the active substance and of the excipients and/or coatings, and the effects on the bioavailability of the active substance which may be caused by the excipient and/or coatings. It is, however, not possible to readily predict whether any particular formulation will provide the desired sustained-release, and it is generally found necessary to carry out considerable experimentation to produce a sustained-release formulation having the desired properties.
The challenge of providing a sustained release delivery system is greatly increased when the patient is an infant, young child, or a more mature person who is unable to easily ingest large tablets or capsules. Such persons are more amenable to the ingestion of pharmaceutical or other active substances via liquid suspensions. The challenge is increased exponentially when for such persons the active compound, which is to be delivered, such as a .beta.-lactam antibiotic, is most effective when protected from acidic gastric juices and is desired to be gradually released in the intestine. These challenges are met by the system for delivery of an active substance which is disclosed herein.